Poster Display & Cocktail e-Poster

13P - A mitigation of breast cancer-induced immune-suppressive tumor microenvironment through curbing miR-155/IL-10/TNF-α loop using a novel quercetin derivative (ID 84)

Presentation Number
13P
Lecture Time
17:30 - 17:30
Speakers
  • Rana A. Youness (Cairo, Egypt)
Session Name
Poster Display & Cocktail
Location
Hall Bordeaux, Palais des Congrès de Paris, Paris, France
Date
Mon, 02.03.2020
Time
17:30 - 18:15
Authors
  • Rana A. Youness (Cairo, Egypt)
  • Amira Abdelmotaal (Abha, Saudi Arabia)

Abstract

Background

Breast cancer (BC) comprises the most prevalent malignancy among females, whilst being the chief cause of cancer-related mortalities. The advent of immunotherapy has opened the gateway towards several therapeutic strategies that surpass the conventional approaches with regards to efficacy and specificity. The most prominent of said strategies is immune checkpoint inhibitors (ICI), which despite its promise has shown evidence of primary and secondary resistance. It has been suggested that the BC-induced immune suppressive tumor microenvironment (TME) can be a definite reason for ICI resistance. As such, we aim to investigate the possible mechanisms of resistance related to TME and probe the administration of a toxicologically safe anti-cancer natural compound known as quercetin-3′-methoxy-3-O-(4″-acetylrhamnoside)-7-O-α-rhamnoside isolated by our group from Cleome droserifolia to alleviate the immune suppressive nature of BC-TME.

Methods

Forty BC patients were recruited in this study. MDA-MB-231 and MCF-7 cells were cultured. IL-10 and TNF-α were measured using Elisa kits. Quercetin glycoside was isolated from C. droserifolia. Cell treatment was performed. RNA was extracted using Bizol. Expression profiles were determined via q-RT-PCR.

Results

BC patients and cell lines showed a marked increase in TNF-α level. Treatment of BC cells with quercetin derivative isolated from C. droserifolia showed resulted in a significant attenuation of the immune-suppressive TNF-α. Nonetheless, the quercetin compound resulted in a concurrent reduction in IL-10 as well. To understand the mechanism of their induced-repression, miR-155 was found to dually direct TNF-α and IL-10. Therefore, miR-155 expression level was probed in BC cells treated with quercetin-derivative where it resulted in a significant modulation of miR-155/IL-10/TNF-α and thus alleviating the immune suppressive TME in BC.

Conclusion

This study provides a potential combinational approach of ICI with a safe natural compound, quercetin-derivative, alleviating BC-induced immune-suppressive TME and thus decreasing the risk of resistance among BC patients.

Legal entity responsible for the study

German University in Cairo.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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